Biology 202
2002 Third Paper
On Serendip

Human behavior is a loosely defined foundation for individuality, generally considered to be influenced and developed by the environment. However, recent molecular studies have exposed genetic factors that suggest a more biological origin for behavior. Gene segments in the genome of humans and other animals have been identified and associated with particular behavioral traits. Is it possible that the presence or absence of even a single gene may predispose one to alcoholism, increased irritability, or enhanced intelligence? Clearly exploration of the nature versus nurture argument with regard to genetic predisposition has social, political, and legal significance.

Employing "behavior" as the experimental variant requires identification of intrinsic behavioral characteristics that may be very difficult to define. Intelligence is considered an expression of behavior, yet the delineation of what makes an individual intelligent has been highly debated. Does IQ determine intelligence? Or is economic success indicative of intelligence? Once an experimenter is comfortable with his proposed definition for a behavior, the characteristic must be reliably and validly measured. However, if the relationship between, for example, intelligence and IQ is not clear, then assigning parameters for levels of intelligence will be even more challenging (1).

Genetically influenced traits tend to be polygenic in character, involving many genes acting in concert to produce a certain response. Therefore, association of one gene with one behavior is usually only partially conclusive. Behavior depends on the interaction of multiple gene sequences with environmental influences. These multiple gene systems are referred to as "quantitative trait loci" (QTL), reflecting their ability to quantitatively distribute phenotypic characteristics. The recently completed human genome sequence has greatly assisted the detection of QTLs and polymorphisms (2). It must also be emphasized that genes do not directly dictate action, but rather are mediated by the proteins that they code for. It is necessary to examine not only the genes but also the assortment of proteins responsible for expression of particular traits (3)It is anticipated that detailed analysis of the human genome will contribute to understandings about gene organization and transcription, and hence regulatory elements that control expression. By utilizing genomic and proteomic tools, the relationship between gene/protein and behavior may be more accurately described.

Effective behavioral genetic research requires investigation of families and populations, rather than individuals. Environmental factors influencing populations must also be considered. The heritability patterns of a behavior are compared with a control population experiencing similar environmental factors. A theoretical formula to account for variability is frequently employed: total phenotypic variability of a specific trait equals the genetic component plus the environmental component plus the interaction of the two (4). However, research has determined that environmental influences tend to disengage behavioral traits among family members rather than unify them. Furthermore, traditional belief asserted that genetic influences were critical only in infancy and early childhood, being superceded by environmental factors during later maturation. Recent genetic-behavioral findings support an opposite conclusion. It appears that the influence of certain genetic traits actually intensify through adolescence (5). Despite attempts to eliminate variability between studied populations, it is virtually impossible to account for the myriad of social experiences contributing to one's unique behavioral profile.

There are several existing indications that support biologically-based behavioral characteristics. Behavior tends to be species specific; varying species of birds utilize different methods for mating and feeding. Behaviors also reproduce themselves in successive generations, or "breed true." This is particularly evident in artificial selection for traits in domestic animals. However, behaviors do change when exposed to altered biological processes. For example, expression of undesirable social manifestations in mental illnesses is commonly controlled with drugs that alter brain chemistry (1).

Behaviors such as mental illness are also found to run in families. In fact, nearly all of the studied behaviors are found to be more heritable than common physical diseases (2). The incidence of schizophrenia in the general population is relatively low, but the siblings of schizophrenics are about 10 times more likely to suffer from the disorder, while the average incidence among children of schizophrenics is about 13 percent. Risks of subsequent generations are comparatively lower. A study investigated the incidence of schizophrenia among fraternal and identical twin populations. Identical twins, who essentially possess identical genomes, maintained a 46 percent rate of tandem schizophrenia. The rate for fraternal twins, however, was only slightly higher than that of non-twin siblings, at an incidence of 14 percent. The exact location of the schizophrenia gene (or genes) has not yet been verified (5).

Most importantly, behavior has an evolutionary history that links related species. The genomes of humans and chimpanzees are genetically very similar, varying principally in organization and assortment of genes. These two populations share traits of highly social primates, including behaviors such as nurturing, cooperation, and altruism. These behavioral characteristics enhance the survivorship of each species (1). Likewise, traits that prove detrimental to a species' survival are eliminated by natural selection. A study performed by Harvard and MIT scientists involved the silencing of the gene responsible for coding of an important enzyme, CAMKII, in lab mice. Mutated mice were found to be unusually aggressive and daring. When placed in an open field, a mutated mouse would dawdle. However, when under the same conditions, a normal mouse would immediately run to the perimeter for cover. The atypical brazen attitude of a mutant mouse would make it much more susceptible to attack by prey in nature. Therefore, this trait is not frequently observed among mouse populations because it has been naturally selected against (6).

Research regarding the genetic influence on obesity has received a lot of media attention. A study in 1994 found that mice possessing the "obese gene" were not only obese, but also suffered from type 2 diabetes and lacked the protein leptin, which acts on the hypothalamus to regulate appetite and energy use. This research was applied to obese children, and several families in the United Kingdom were found to be leptin deficient. Children were obese as long as food was available for their consumption (7). It has been suggested that the obesity and type 2 diabetes epidemics among American children has an bio-evolutionary component. Simply, humans have old genes in a new environment. Our species evolved to sustain a hunting-gathering lifestyle with frequent famine and mandatory physical activity for survival. Food is made readily available in our society, and many children are become increasingly less physically active. Unfortunately, the genes governing metabolism have not changed to accommodate this indulgent, inactive lifestyle. It has been estimated that genetics contributes to about 40 percent of obesity variance, while over 200 genes and gene markers for obesity have been identified (8). This is a classic example of how both environmental and biological factors are influencing behavior.

A rare genetically based neurodevelopmental disorder, Williams Syndrome (WS), may provide the most compelling evidence for parallel functional networks within the brain, as well as expose how these functions are influenced by genetic processes during neurodevelopment. WS is caused by a micro-deletion on the long arm of chromosome 7 (7q.11.23) with an incidence of 1 in 20,000 live births. This deletion encompasses a 1.5 mega base chromosomal segment, coding for an estimated 17 genes, and is thought to occur by unequal recombination during meiosis. The deleted segment includes elastin (ELN) and four genes that are understood to be highly expressed in the brain (FZD9, STXIA, LIMK1, CYLN2) (9).

WS is associated with multiple morphological and physiological manifestations. In addition to distinctive facial characteristics, WS is identified with cardiac problems, particularly supravalvular aortic stenosis, peripheral pulmonary stenosis, and hypertrophy. Other physical issues in WS include additional vessel narrowing, lax joints, joint contractures, hernias, short stature, and a hoarse voice. It is suspected that the ELN deletion is responsible for these connective tissue problems (9). Although the incidence of premature death due to cardiovascular and other organ complications in WS has been reported to be moderately high, contemporary methods of specialized and vigilant medical care have greatly improved and increased the lives of WS individuals (10).

The WS cognitive profile is particularly intriguing. Affected individuals possess a social-emotional phenotype that includes unusually elevated sociability and empathy coupled with a fervent attraction to music, probably due to emotional factors. WSI are associated with gregarious and loquacious personalities, involving excessive sociability with strangers. The disparity between cognitive strengths and weaknesses in the WS profile is considerable. The average IQ s of WS individuals (WSI) is fairly depressed, averaging at about 60. However, variation among WSI does exist and IQ s as high as 100 have been measured. WSI demonstrate great strengths with face perception and recognition memory, affective prosody, short-term auditory memory, and select aspects of languages, despite functioning in the range of mild mental retardation. However, individuals struggle with visuospatial, motor, vasomotor integration, and arithmetic skills. WSI can maintain differences between verbal and non-verbal skills that exceed two or three standard deviations on standardized measures. Overall language abilities are delayed, but phonological processing, verbal fluency, vocabulary, and morpho-syntax are impeccably developed (9).

Whole brain volumes in WS are about 15 percent smaller than normal. However, the superior temporal gyrus, which contains the primary auditory cortex and regions associated with auditory inputs necessary for language and music processing, are within normal volumes. Alteration of function in this area may explain the high rate of hyperacusis in WS, as well as involve the signature language and musical perceptions. An exaggerated leftward symmetry of the planum temporale is also observed. This pronunciation has been observed in musicians with perfect pitch and is linked to hemispheric dominance for language (9). A particular portion of the midline cerebella vermis is considerably larger than in the unaffected population. A growing body of evidence suggests that the neo-cerebellum participates in higher cognitive function, particularly with regard to fluent speech (11). The fore mentioned neurological peculiarities not only demonstrate how altered genetics in WS is closely related to language and musical abilities, but also suggest that a broad range of variation in diverse brain regions contribute to the unique characteristics of WS.

WS and autism are frequently compared to elucidate key neurological concepts. Autism is essentially the converse of WS, in that it involves low sociability, lessened empathy, and deficits in face recognition and non-verbal features of communication. Individuals suffering from autism fail to engage the fusiform gyrus (FG) during face perception exercises. However, preliminary evidence supports that WSI are normal in their engagement of the FG during corresponding exercises (9). Therefore, evaluation of WS not only reveals various neurological functions that are affected by the gene deletion, but also shed light into how the brain operates in other neurodevelopmental disorders. Neural systems employed by WSI for sensory, cognitive, and language processing is not identical to systems employed by the unaffected population for the same tasks (11). It is possible that the systems mediating behavior in WS may be mechanistically and anatomically distinct from the norm; high linguistic functions are maintained despite severe general cognitive deficits.

My interactions with Williams Syndrome children and adults have provided insight into their individual similarities and diversities. In July of 2000 the International Williams Syndrome Conference was held in Michigan, featuring both human genetics professionals and WSI accompanied by their families. The ages of WSI ranged from infancy to late adulthood. Although they all maintained characteristic morphological features, there was a substantial degree of unique physical difference in each person. Similarly, the presence of organ involvement varied among individuals.

Being surrounded by hundreds of WSI provided me with plenty of opportunity to socially interact with them, as well as allowing them to interact with each other. Conversation with a WSI is sometimes described as typical "cocktail conversation." Often times one unfamiliar with the disorder will not detect any social disparity. WSI have mastered their linguistic abilities and not only use an impressive vocabulary, but also exercise flawless syntax and grammatical complexity (12). However, their gregarious and trusting nature frequently leads them to become inappropriately friendly or even affectionate with strangers. In fact, the parents of young WSI are encouraged to reprimand their children when they exhibit this behavior. This emphasizes how innate this affability is in WS. A common conversation between two WSI during the conference involved countless superlatives and repeated affectionate gestures such as hugging or holding hands.

On the last evening of the conference, a banquet and dance was held for all participants. WSI of all ages engaged in singing and dancing, as long as the music was not played too loudly (hyperacusis). At one point, a young girl injured her foot while on the dance floor and began to cry. Immediately dozens of WSI surrounded her, providing kisses, hugs, and comforting words. A number of others were so affected by the misfortune of the young girl that they began to cry as well. This episode lasted for about fifteen minutes, and then the celebration resumed. These experiences demonstrated how unusually compassionate and concerned this cohort is toward people they barely know (or are not acquainted with at all).

The basic function and organization of the WS brain preserves linguistic abilities associated with higher cognitive function. It may be concluded that there exists a disproportionate conservation of the most autonomous aspects of human linguistic processing in this gene deletion. Particular social and musical affinities are also exhibited by those who possess the WS gene deletion. However, great variation between and among WS populations does exist. Not all WSI are musically inclined, nor are they all equally socially engaged. Likewise, the ELN gene deletion exists in all WSI, but not all suffer from the cardiovascular or other connective tissue manifestations.

To possess the genes for obesity does not automatically condemn one to a life-long battle with weight gain, but in many cases does predispose an individual to metabolic struggles. WS may be used as a convincing example of genes affecting behavioral traits. By utilizing the method of attacking "smaller rocks" to reach the mountain, the mysteries of genes and behavior may be revealed. Genes do not code for behavior, but rather proteins. In researching the translation and function of these proteins, and perhaps any neurological interactions, the scientific world may uncover the fundamentals of human behavior. The genes equal behavior presumption seems no less assuming than brain equaling behavior: genes, after all, are responsible for the function and organization of the brain.

References

1) What is behavioral genetics?
4) Evolution: Genetics and Behavior

5) Recent Developments in Human Behavioral Genetics: Past Accomplishments and Future Directions

6) The Maniacal Mouse: Linking Genetics and Behavior

7) Genes Do Play a Role in Obesity

8) Is Obesity Grounded in Genetics or Behavior-- or Both?

9) Genetics of Childhood Disorders: Williams Syndrome and Brain-Behavior Relationships

10) Deering, R., Kaplan, P., Nicholson, S. Williams Syndrome and Anesthesia: Evaluation of a Large Unselected Cohort. Presented at the Williams Syndrome Conference in MI (2000). In publication, Journal of Pediatrics.

11) Williams Syndrome: An Unusual Neuropsychological Profile

12) Williams Syndrome: From Brain to Cognition

2) Toward Behavioral Genomics

3) Genes and Behavior: A Complex Relationship


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